The background description provided herein is for the purpose of generally presenting the context of the present invention. The subject matter discussed in the background of the invention section should not be assumed to be prior art merely as a result of its mention in the background of the invention section. Similarly, a problem mentioned in the background of the invention section or associated with the subject matter of the background of the invention section should not be assumed to have been previously recognized in the prior art. The subject matter in the background of the invention section merely represents different approaches, which in and of themselves may also be inventions. Work of the presently named inventors, to the extent it is described in the background of the invention section, as well as aspects of the description that may not otherwise qualify as prior art at the time of filing, are neither expressly nor impliedly admitted as prior art against the present invention.
Ion mobility spectrometry is a chemical and biological detector that distinguishes and selects ions quickly. In the recent years, the world pays more and more attention on looking for the sensitive detector that is convenient to carry, easy to use and fast to detect in order to protect the continental safety from drug and ordnance smuggling. Due to the high performance of ion mobility spectrometry in such areas, people have developed great interest in researching ion mobility technology and ion mobility spectrometry's performance has been gradually improved these years. Meanwhile, the requirement of applying ion mobility spectrometry in different conditions is becoming more specific and strict. Besides, since the separation mechanism of ion mobility spectrometry is based on the difference of ion mobility in gas phase whose nature is size and shape of ion, ion mobility spectrometry has provided another method of separating that is different from mass spectrometry or chromatography. Traditional practice of ion mobility spectrometry with mass spectrometry or chromatography has improved the performance of individual detector and has lowered the frequency of false positive. Also, ion mobility spectrometry can be used to detect the size of ion so it has great contribute in analyzing the atmosphere aerosol and big biological molecules (like proteomics), It shows great potential in researching and analyzing.
Nowadays, there are two main types of on mobility spectrometry detectors that are put in commercial use: on mobility spectrometer (IMS) and differential mobility spectrometer (DMS). For the first one, the most typical setting is to stack many ring electrodes and isolate them in order to construct the so called drift tube and fill with gas into it up to some certain pressure (usually 1-20 Torr). The stacked ring electrodes have been applied with longitudinal voltage so an axial electric field is formed insider the drift tube. Under the effect of electric field and the collision with neutral molecules, there are directional movements in axial direction besides diffusion. According to ion mobility function:{right arrow over (v)}=K{right arrow over (E)},where {right arrow over (v)} is the drift velocity of ion; K is the ion mobility; {right arrow over (E)} is the strength of electric field.
Under the same electric field, due to different mobility of ions, the velocities of ions are different so the time spent in drift tube is different. Different ions are separated based on that. For the second one (DMS), the mechanism of separation of ions is different from the first one. It is not based on the difference of ion mobility but based on the nonlinear change of mobility under electric fields of different strengths. The nonlinear change of mobility is different from ion to ion so DMS can separate ions based on difference of mobility caused by high and low electric fields. Because of simple structure of DMS, the simplest structure of which only consists of two shaft sleeves or two parallel plate electrodes, it is commonly used in developing portable or small devices. Moreover, DMS can work under atmospheric condition without the use of vacuum pump. However, due to the complexity of separation mechanism, its mobility spectrum is hard to take a clear interpretation, there is no extensively recognized way in interpreting such mobility spectrum. Other than two kinds of ion mobility devices previously described, there is another device that is based on separation of mobility is commonly used and called differential mobility analyzer (DMA). The basic structure of DMA is based on the vertical electric filed between two parallel plate electrodes and the drift gas between the plate electrodes in longitudinal direction. Tons enter from the entrance of one plate electrode. When ions enter the drift region between plate electrodes, the overall movement of ions can be divided into two components: movement in the direction of drift gas with the same speed as drift gas and movement in the direction of electric field which is vertical to the direction of ion flow. Based on the ion mobility function, different ions have different speed in the vertical direction so the time ions spent passing the cross-section of drift gas is different which causes the different horizontal distance from entrance when ion reaches opposite plate electrode. However, because of the limitation of the structure of DMA itself and the affection of ion diffusion, the ability of separation of ions is difficult to improve, Usually, tens of resolution or even less its maximum yield so this is not quite an area people are interested in. On the other hand, IMS can reach much higher resolution through longer drift distance or stronger electric field theoretically. Actually, People are trying different methods to improve the performance of IMS.
Alan L. Rockwood and his colleagues from Brigham Young University have demonstrated their patent of cross flow ion mobility spectrometry (U.S. Pat. No. 7,199,362B2) applied in USA. They put drift gas in both radial and axial directions and put electric field in opposite radial direction of drift gas to balance the effect of drift gas. The can make ions with appropriate mobility balanced in the axial direction, hereby realize the correct selection of appropriate ions. Meanwhile, the axial drift gas is transferring ions to next unit or detector. However, the control of drift gas in the axial and radial directions can be tough so the resolution is relatively low. Satoshi Ichimura from Hitachi has mentioned a counter flow ion mobility spectrometry in their patent US20030213903A1 applied in USA. They change the speed of inner drift gas by gradually reducing the inner diameter of drift tube and make the opposite electric filed counteract the effect of drift gas. Thus, different ions with different mobility will stay in different positions across the axial direction and hereby can be separated. However, this method can't constrict the diffusion of ions in radial directions, the huge loss of ions makes detection difficult.
In fact, the idea of using drift gas and opposite electric field to realize the separation/accumulation of ions has been mentioned by J. Zeleny (J. Zeleny, Philos. Mag., 1898, 46, 120-154) in the concept of parallel flow ion mobility spectrometry. This method makes drift gas pass through two parallel grid electrodes and set opposite electric fields between two parallel electrodes, Based on the ion mobility equation, ions with appropriate mobility are captured because their drift velocity is the same as but opposite to that of the drift gas. Other ions are blown off because of inappropriate mobility. Theoretically, this method can separate ions with small mobility differences under relatively low speed of drift gas and weak electric field, Thus, it has good selectivity of ions. However, it is very difficult to introduce ions and also requires very stable drift gas and electric field. Moreover, its characteristics time consuming makes serious ion diffusion that consequently ruins the high sensitivity detection. At last, there is no practical prototype developed. Victor V. Laiko (Victor V. Laiko, J Am Soc Mass Spectrum, 2006, 17, 500-507) has put his effort in theoretical analysis of parallel flow ion mobility spectrometry. He separately developed the formulas of resolution and ion diffusion affected by drift gas and electric fields. Meanwhile, Laiko developed the simulation model to introduce ions into device vertically and then used the numerical analysis method to run simulation test. The result was glad and high resolution was obtained but there is no further experimental result, Obviously, the experiment of this kind must be very difficult to do, Wenjian Sun has announced a device that can be used to separate or accumulate ions in the World Patent WO2010060380. This device has good selectivity of ions by using drift gas and opposite electric fields, meanwhile, accumulating ions.
Alexander Loboda (Alexander Loboda, J Am Soc MassSpectrom 2006, 17, 691-699) from PerkinElmer SCIEX has made a device called counter flow ion mobility device by using segmented quadrupole ion guide and coupled it to an orthogonal injection time of flight (TOF) mass spectrometer. The difference of this ion mobility analyzer from Ichimura's counter flow ion mobility device is that this device does not capture ions at all but uses a counter flow of gas to counteract the force exerted by the electric field. Thus, both of the drift time and the voltage drop over the drift region can be increased. It can not only improve the resolution but also expand the time width of ion peak which extremely elevates the sampling frequency of TOF. This device can reach relatively high resolution in a low atmosphere pressure condition. However, because of the limited length of the drift region, the device's maximum resolution is limited, Although elevating gas pressure can help broaden the retention time of ions and also improve the device's performance, the ion diffusion in the radial direction is out of control. Moreover, the device selects ions by the interaction effect of drift gas and electric fields so the resolving ability of device mainly results from the stability of drift gas and electric fields. In facts, it is very hard to obtain the stable drift gas and electric field.
Kevin Giles (Rapid Common. Mss Spectrum., 2004, 18, 2401-2414) and his colleagues have disclosed a kind of travelling wave ion mobility spectrometry, it causes the difference in strength of local electric field in the drift tube by generating electric pulse in the axial direction in the traditional drift tube ion mobility spectrometry, Ions move forward when the electronic pulses are approaching. Because of different mobility of ions, the distances ions pass through are different. When electronic pulses pass over the ions periodically, the ion groups in axial direction will then be separated due to many times of tiny difference of tiny difference of forward movement. Unlike the traditional on mobility spectrometry, the travelling wave ion mobility spectrometry does not depend on voltage difference between the two ends of drift tube to separate ions but uses local intense electric field in the drift tube to separate ions in a short time again and again so it can realize relatively high resolving power by using relatively low voltage difference. It is considered to be a good ion mobility analyzer and it has been applied on the IMS-MS device of Synapt series provided by Waters Corporation. However, due to the mechanism of separation by travelling wave ion mobility spectrometry and the complexity of separation process, it is hard to get the information about ion mobility or collisional cross section directly from the spectrum.
Other than that, David E. Clemmer (Anal. Chem., 2009, 81, 1482-1497) and his colleagues have disclosed a kind of ion cyclotron mobility spectrometry in which the whole drift tube has eight segments, four bent drift tubes and four ion funnels. The alternative connection of bent drift tubes and ion funnels forms a closed ion cyclotron structure. The ions are urged forward in the drift by the electric field that is generated by a pulse power supply with a certain frequency. When the drift time of ions with certain mobility matches the frequency of the drift electric field, this kind of ions will survive with highest survival percentage in each segment. After experiencing many times of periodic and continuous separation, only ions with appropriate mobility can stay at last. Theoretically, this device can achieve very high ion resolution. However, because of long separation time and ion diffusion in the radial direction, only one kind of ions can survive. The loss of ions is huge which makes sensitivity relatively low. On the other hand, Robert. Harold Bateman has mentioned a kind of ion mobility spectrometry with closed loop structure in the US patent publication No. US20090014641A1. Except for joining the front and rear ends of traditional drift tube together as well as imposing radial confinement field, it is not so special. Particularly, it has adopted an ion path with the pattern of folding loop. Thus, for solving the problem of continuous voltage increment of each segment in the ion drift process, one of segments has to be floated electrically while ions drift in the loop. The work principle by floating the voltage of the segment is similar with that of navigation lock. This may cut away part of the ion cloud and bring uncertain effect on the drift time of ions.
So far, we have demonstrated some developing technologies of ion mobility analyzer. High performance ion mobility analyzer that needs long drift distance requires rapid switching speed of voltage signals to ensure reasonable voltage value of each electrode. On the other hand, the existing ion mobility storage devices that use low electric field needs to balance drift gas and electric field in order to store ions. Unfortunately, drift gas can't be adjusted in a fast, cheap, stable and accurate way like electric field so ion mobility storage device with high resolution is difficult to achieve.